System for non-invasive heart treatment

ABSTRACT

The invention provides a non-invasive method for treatment of arrhythmia. In a first aspect, a method for treatment of atrial fibrillation in a heart of a patient comprises directing radiation from outside the patient toward one or more target treatment regions of the heart so as to inhibit the atrial fibrillation. The radiation may induce isolation of a pulmonary vein.

CROSS-REFERENCES TO RELATED APPLICATIONS

This is a continuation patent application which claims priority fromU.S. patent application Ser. No. 10/651,764 filed on Aug. 23, 2003,which claims the benefit under 35 USC 119(e) of U.S. Provisional PatentApplication No. 60/438,876 filed on Jan. 8, 2003, and of U.S.Provisional Patent Application No. 60/445,716 filed on Feb. 7, 2003, thefull disclosures of which are incorporated herein by reference.

STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSOREDRESEARCH OR DEVELOPMENT

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REFERENCE TO A “SEQUENCE LISTING,” A TABLE, OR A COMPUTER PROGRAMLISTING APPENDIX SUBMITTED ON A COMPACT DISK.

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BACKGROUND OF THE INVENTION

The present invention is generally related to treatment of arrhythmia,and in one embodiment provides a non-invasive treatment of arrhythmiahaving long-term efficacy.

A typical adult human heart beats at a rate of about 70 beats perminute. The rate is not constant, however, and changes during andfollowing exercise, with fear or anxiety, or for other reasons. A heartcan also pump arrhythmically for many reasons, including damage to theheart's electrical conduction system. Arrhythmias interfere with theheart's ability to pump blood, and can result in severe symptoms,including death.

Atrial fibrillation is one of the most common cardiac arrhythmias.Atrial fibrillation occurs in as many 50% of patients undergoing cardiacoperations. Patients with chronic Atrial Fibrillation may suffer fromsymptomatic tachycardia or low cardiac output, have a risk ofthromboembolic complications, and are at risk for death. Until just afew years ago many health care providers thought atrial fibrillation tobe a “nuisance” arrhythmia with few consequences. However, medicalresearch has uncovered some devastating complications, including stroke,congestive heart failure, and cardiomyopathy. Many conditions have beenassociated with atrial fibrillation, including thyroid disorders, valvedisease, hypertension, sick sinus syndrome, paricarditis, lung disease,and congenital heart defects. Atrial fibrillation can occur at any age,but its prevalence tends to increase with age and effects men slightlymore often than women.

During Atrial Fibrillation, the atria lose their organized pumpingaction. In normal sinus rhythm, the atria contract, the valves open, andblood fills the ventricles (the lower chambers). The ventricles thencontract to complete the organized cycle of each heart beat. Atrialfibrillation has been characterized as a storm of electrical energy thattravels across the atria, causing these upper chambers of the heart toquiver or fibrillate. During Atrial Fibrillation, the blood is not ableto empty efficiently from the atria into the ventricles with each heartbeat. Blood can then pool and become stagnant in the atria, creating asite for blood clot formation. Such clot formation can become a primarysource of stroke in patients with Atrial Fibrillation.

Non-surgical treatments are sometimes effective in treating atrialfibrillation. Several drugs are known, but may have significant sideeffects and are not ideal for treatment of acute fibrillation.Pharmacological therapies are also associated with adverse effects in asignificant proportion of patients. Moreover, although electricalcardioversion (alone or in combination with anti-arrhythmic therapy) isoften effective in restoring sinus rhythm, high recurrence rates ofatrial fibrillation have been reported.

A number of invasive surgical procedures have been proposed fortreatment of Atrial Fibrillation. Invasive procedures involving directvisualization of the tissues include the Maze procedure. Dr. James Coxand others proposed the original Cox-Maze procedure in which the atriaare surgically dissected and then repaired. In the Maze procedure, forexample, ectopic re-entry pathways of the atria are interrupted by thescar tissue formed using a scalpel or the like. The pattern of scartissue prevented recirculating electrical signals which can result inatrial fibrillation.

The Maze surgical procedure has been simplified by the use ofcryoprobes, radio frequency (RF) probes, and laser probes to effect thepattern of scar tissue. For example, ablation is sometimes used toterminate arrhythmias by introducing a catheter into the heart anddirecting energy at specific areas of heart tissue. By using atransarterial catheter to deliver the energy to the atria underfluoroscopy, interventional cardiologists have treated atrialfibrillation in a less-invasive manner. RF energy has been usedsuccessfully to terminate arrhythmias by introducing the catheter intothe heart and directing the RF energy at specific areas of the hearttissue. Nonetheless, there is still a need for potentially non-invasivetreatments of arrhythmia having long-term efficacy.

BRIEF SUMMARY OF THE INVENTION

The present invention provides non-invasive methods for treatment ofarrhythmia.

In a first aspect, the invention provides a method for treatment ofatrial fibrillation in a heart of a patient. The method comprisesdirecting radiation from outside the patient toward one or more targettreatment regions of the heart so as to inhibit the atrial fibrillation.

The radiation from outside the patient may induce isolation of apulmonary vein, often effecting bilateral pulmonary vein isolation. Inmany embodiments, the radiation results in a formation of at least onelesion in the heart. The lesion can block conduction with or encirclethe pulmonary vein, although a lesion maturation time may be presentbetween directing of the radiation and isolation of the pulmonary vein.As atrial fibrillation often propagates from the pulmonary vein, thelesion can induce sufficient electrical isolation of the first pulmonaryvein from adjacent electrical pathways of the heart such that the atrialfibrillation is inhibited. The radiation will often be directed to thetarget region(s) from a plurality of angles so as to avoid exceeding atolerance of adjacent tissues.

At least one ectopic focus of the heart may be targeted for treatmentwith the radiation. The radiation may ablate linear lesions within theheart so as to inhibit an ectopic electrical pathway. The lesions maycorrespond to a Maze lesion pattern.

A first portion of the radiation may be directed to the patient in afirst treatment, with a second portion of the radiation directed to thepatient in a second treatment. Hence, the invention can accommodatefractionated radiation procedures for inhibition of Atrial Fibrillation.The patient may be assessed between the first and second treatmentsallowing the second treatment to be elected based on the assessment ofthe first treatment.

In many embodiments, the radiation can be delivered as a series ofradiation beams extending toward the heart from different angles. Theradiation beams may be dynamically registered with the one or moreregions of the heart. The dynamic registration may be performed so as tocompensate for pumping of the heart, and/or to compensate for movementof the patient and breathing. The radiation source may be moved aroundthe patient by a robot arm, and the radiation may be directed toward theregion of the heart from the radiation source along the series ofradiation beams.

A plurality of target adjustment images may be acquired during theradiation treatment procedure. A position of the region(s) relative to areference frame of the robot may be acquired from the target adjustmentimages. Radiopaque fiducial markers may be inserted to the patientaround the region(s). The target images may be acquired with first andsecond fluoroscopic systems, and the target adjustment images may beacquired between delivery of successive radiation beams. The robot armmay move the source of radiation with six degrees of freedom.

The patient anatomy may be scanned so as to identify the targetregion(s), and the series of radiation beams may be planned, oftenbefore initiating treatment. Scanning the patient anatomy may comprise aComputer Tomography (CT) scan, a Magnetic Resonance Image (MRI) scan,sonography, or the like. Planning the series of radiation beams maycomprise determining a number, intensity, and direction of the radiationbeams. Planning of the target region may comprise determining a targetregion shape, with the radiation delivered so as to effect anon-isocentric treatment.

The radiation may be generated with a portable linear accelerator, theradiation often comprising x-ray radiation. Alternatively, the radiationmay comprise gamma radiation. Other suitable types of radiation may alsobe employed, including various types of particle beams.

In another aspect, the invention provides a method for treatment ofAtrial Fibrillation in a heart of patient. The method comprisesdirecting a series of radiation beams from outside the patient and fromdifferent angles toward a target treatment region of the heart. Theradiation beams are dynamically registered with the treatment region,and the irradiation of the target treatment region effects isolation ofa first pulmonary vein so as to inhibit the Atrial Fibrillation.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of a radiation treatment system.

FIG. 2 is a schematic illustration of a simplified Maze lesion pattern.

FIG. 3A-3D illustrate alternative patterns of lesions in the heart fortreatment of arrhythmia.

FIG. 4 illustrates stereotactic radiosurgery using the system of FIG. 1.

FIG. 5 is a flowchart schematically illustrating a radiosurgerytreatment method.

DETAILED DESCRIPTION OF THE INVENTION

Radiosurgery is a known method of treating tumors in the body. Theradiation can be delivered invasively in conjunction with traditionalscalpel surgery, or through a percutaneous catheter. Radiation can alsobe delivered non-invasively from outside the body, through overlyingtissue. Advances in stereotactic surgery have provided increasedaccuracy in registering the position of tissue targeted for treatmentand a radiation source. For example, see U.S. Pat. Nos. 6,351,662 and6,402,762. Stereotactic radiosurgery systems may be commerciallyavailable from ACCURAY, INC. of Sunnyvale, Calif., and BRAINLAB. TheAccuray Cyberknife™ stereotactic radiosurgery system has reportedly beenused to provide targeted, painless, and fast treatment of tumors.

An exemplary Cyberknife stereotactic radiosurgery system 10 isillustrated in FIG. 1. Radiosurgery system 10 has a single source ofradiation, which moves about relative to a patient. Radiosurgery system10 includes a lightweight linear accelerator 12 mounted to a highlymaneuverable robotic arm 14. An image guidance system 16 uses imageregistration techniques to determine the treatment site coordinates withrespect to linear accelerator 12, and transmits the target coordinatesto robot arm 14 which then directs a radiation beam to the treatmentsite. When the target moves, system 10 detects the change and correctsthe beam pointing in near real-time. Near real-time image guidance mayavoid any need for skeletal fixation to rigidly immobilize the target.

Improvements in imaging and computer technology have led to advances inradiation treatment, often for targeting tumors of the spine and brain.The introduction of CT scanners enables surgeons and radiationoncologist to better define the location and shape of a tumor. Furtherimprovements in imaging technology include MRI and PET scanners. Inaddition, radiation therapy has also been aided by enhancements inancillary technologies such as simulators to help position patients andadvanced computers to improve treatment planning to enable the radiationoncologist to deliver radiation from a number of different angles.Computer technology has been introduced that enable radiationoncologists to link CT scanners to radiation therapy, making treatmentmore precise and treatment planning faster and more accurate, therebymaking more complex plans available. Such advancements allow integratedconformal therapy, in which the radiation beam conforms to an actualshape of a tumor to minimize collateral damage to the surroundinghealthy tissue. By combining simulators and imaging and treatmentplanning computers, the irradiation can be precisely administered.

System 10 makes use of robot arm 14 and linear accelerator 12 undercomputer control. Image guidance system 16 can monitor patient movementand automatically adjust system 10 to maintain radiation registrationwith the selected target tissue. Rather than make use of radiosurgerysystem 10 and related externally applied radiosurgical techniques totumors of the spine and brain tissues, the invention applies system 10to numerous cardiac conditions, and in one exemplary method to thetreatment of Atrial Fibrillation.

Tradition radiosurgery instruments without image guidance technologyrely on stereotactic metal frames screwed into the patient's skull toaccurately target a tumor. Traditional radiosurgery has its drawbacks,the biggest of which relate to the use of the frame, including the painand difficulty of accurately reattaching the frame in precisely the samelocation, along with the inability to target tissues other than those inthe neck and head. Conventional linear accelerators for these systemscan also be the size and weight of an automobile. Frame-basedradiosurgery is generally limited to isocentric or spherical targettreatments. To allow a device which can precisely pinpoint and treattissues throughout the body, system 10 makes use of a portable linearaccelerator, such as those originally designed for industrialinspections, which can be carried on a person's back. Linearaccelerators may be commercially available from SCHONBERG RESEARCHGROUP, SIEMENS, PICKER INTERNATIONAL INC. or VARIAN.

System 10 allows intensity modulated radiation therapy. Usingcomputerized planning and delivery, intensity modulated radiationtherapy conforms the radiation to the shape of (for example) a tumor. Byusing computers to analyze the treatment planning options, multiplebeams of radiation match the shape of the tumor. To allow radiosurgery,system 10 can apply intense doses of high-energy radiation to destroytissue in a single treatment. Radiosurgery with system 10 uses precisespatial localization and large numbers of cross-fired radiation beams.Because of the high dosage of radiation being administered, suchradiosurgery is generally more precise than other radiation treatments,with targeting accuracies of 1 to 2 mm.

Linear accelerator 12 is robotically controlled and delivers pin-pointradiation to target regions throughout the body of the patient.Radiation may be administered by using a portable linear acceleratorsuch as that illustrated in FIG. 1. Larger linear accelerators may alsogenerate the radiation in some embodiments. Such linear accelerators maybe mounted on a large rotating arm that travels around the patient,delivering radiation in constant arcs. This process delivers radiationto the target tissue and also irradiates a certain amount of surroundingtissue. As a result, such radiation therapy may be administered in aseries of relatively small doses given daily over a period of severalweeks, a process referred to as fractionation. Each radiation dose cancreate some collateral damage to the healthy surrounding tissue.

In the exemplary embodiment, robot arm 14 of system 10 is part of a purerobotics system, providing six degree of freedom range of motion. Inuse, the surgeon basically pushes a button and the non-invasiveprocedure is performed automatically with the image guidance systemcontinuously checking and re-checking the position of the target tissueand the precision with which linear accelerator 12 is firing radiationat the tumor. Image guidance system 16 provides x-ray image guidancethat gives the surgeon the position of internal organs and skeletalanatomy. Image guidance system 16 continuously checks, during aprocedure, that the target is at the same place at the end of thetreatment that it was at the beginning. The exemplary image guidancesystem included with the Accuray CyberKnife™ radiosurgery system takesthe surgeon's hand out of the loop. The surgeon may not even be in theoperating room with the patient. Instead, the image guidance systemguides the procedure automatically on a real-time basis. By combiningadvanced image guidance and robotics, system 10 has proven effective intreating head and neck tumors without having to resort to stereotacticmetal frame screwed into the skull of a patient.

Image guidance system 16 includes diagnostic x-ray sources 18 and imagedetectors 20, this imaging hardware comprising two fixed diagnosticsfluoroscopes. These fluoroscopes provide a stationary frame of referencefor locating the patient's anatomy, which, in turn, has a knownrelationship to the reference frame of robot arm 14 and linearaccelerator 12. System 10 can determine the location of the skull orspine in the frame of reference of the radiation delivery system bycomparing digitally reconstructed radiographs derived from the treatmentplanning images with radiographs acquired by the real-time imagingsystems of the fluoroscopes.

Once the skeletal position is determined, the coordinates are relayed torobot arm 14, which adjusts the pointing of linear accelerator 12 andradiation is delivered. The speed of the imaging process allows thesystem to detect and adjust to changes in target position in less thanone second. The linear accelerator is then moved to a new position andthe process is repeated. Alternative systems may make use of lasertriangulation, which refers to a method of using so-called laser tattoosto mark external points on the skin's surface so as to target thelocation of internal organs and critical structures. An alternativesystem commercialized by BRAINLAB uses a slightly different approachthat measures chest wall movements.

The exemplary CyberKnife™ radiosurgery system is currently available fortreatment of lesions throughout the cervical spine. These lesions may bebenign or malignant, such as metastasis, meningiomas, and arterialvenous malformations, the CyberKnife™ radiosurgery system has been usedto successfully treat metastic lesions in patients who are otherwise notcandidates for surgery or lesions which are not amenable to opentechniques. Progress has also been reported in developing theCyberKnife™ radiosurgery system for use in the thoracic and lumbarregions as well, with preliminary experience being indicated aspromising. System 10 combines robotics and advanced image-guidance todeliver true frameless radiosurgery. Multiple beams of image guidedradiation are delivered by robot arm 14 mounted linear accelerator 12.The radiation can converge upon a tumor, destroying it while minimizingexposure to surrounding healthy tissue. Elimination of a stereotacticframe through the use of image guided robotics enables system 10 totreat targets located throughout the body, not just in the head.Radiosurgery is thus possible in areas such as the spine that havetraditionally been difficult to treat in the past with radiosurgery, andfor pediatric patients such as infants, whose skulls are too thin andfragile to undergo frame-based treatment.

System 10 allows ablation anywhere in the patient's body. Theimage-guidance system tracks bony landmarks of the skull to targetradiation accurately. For body treatments, the image-guidance trackssmall markers or fiducials percutaneously implanted in the tumor totarget radiation. Advantages of system 10 include a treatment which canbe provided on an outpatient basis, providing a painless option withoutthe risk of complications associated with open surgery. Treatment may beapplied in a single-fraction or hypo-fractionated radiosurgery (usually2 to 5 fractions) for treatment near sensitive structures. System 10provides flexibility in approach through computer control of flexiblerobotic arm 14 for access to hard-to-reach locations. System 10 alsoallows isocentric (for spherical) or non-isocentric (for irregularlyshaped) treatments. Through the use of robotic arm 14, harm to thecritical structures surrounding a lesion may be reduced. After carefulplanning, the precise robotic arm can stretch to hard-to-reach areas.The precise radiation delivered from the arm then minimizes the chanceof injury to critical surrounding structures, with near-real-timeimage-guidance system 16 eliminating the need for rigid immobilization,allowing robot arm 12 to track the body throughout the treatment.

Referring now to FIG. 2, Cox and his colleagues first described the Mazeprocedure for treatment of atrial fibrillation. In the original Mazeprocedure, ectopic re-entry pathways of the atria are interrupted byintroducing scar tissue using a scalpel. In FIG. 2, a simple Maze pathis conceptually illustrated. Maze lesion pattern 30 has one entrance 32,one exit 34, and one through path 36 with multiple blind alleys 38.Since the initial description of the Maze procedure by Cox andcolleagues, a number of related open surgical approaches have beendevised for the treatment of atrial fibrillation. Although successful inthe irradication of atrial fibrillation in a high percentage of cases,these procedures are invasive, requiring median sternotomy,cardiopulmonary bypass, cardioplegic arrest, extensive cardiacdissection, and/or multiple atrial incisions. These procedures are alsoassociated with significant morbidity. There are a number of iterationsof the Cox procedure, including the Cox-Maze III procedure. While thisoperation has proven to be effective, it has significant shortcomings.The performance of the Cox-Maze III procedure requires cardiopulmonarybypass and an arrested heart. In most hands, it adds significantly tothe cross-clamp time. Because of its perceived difficulty, few surgeonshave learned to perform this operation. Finally, there is significantmorbidity, particularly in terms of pacemaker requirements. Theseproblems have led researchers to evaluate strategies to simplify thesurgical treatment of atrial fibrillation.

It has been suggested that in many patients, atrial fibrillation may becaused by re-entry wavelets limited to specific areas near the originsof the pulmonary veins. Success has also been reported with more limitedprocedures aimed at electrical isolation with discreet atrial lesions,utilizing atriotomy, radiofrequency ablation, or cryoablation. As can beunderstood with reference to FIGS. 3A through 3D, alternative approacheshave involved both investigating different lesion sets and using avariety of energy sources to create linear lesions of ablation toreplace the more time-consuming surgical incisions. These newerprocedures have the potential to decrease the procedure time byeliminating the extensive sewing associated with the many atrialincisions of the traditional Cox-Maze III procedure. A number ofdifferent technologies have been adopted to achieve this strategy. Theseinclude cryoablation, unipolar and bipolar RF energy, microwave energy,laser energy, and ultrasound. In general, the goals of atrialfibrillation ablation are to cure atrial fibrillation by creating linearlines of conduction block in the atria to replace the surgicalincisions. These principally apply endocardial ablation in the beatingheart, with most devices involving heating the tissue to causecoagulation necrosis.

Catheter-based atrial fibrillation ablation allows a less invasiveapproach, shortens operative time, and simplifies the operation. Thisreduces morbidity and mortality of the atrial fibrillation surgery,allowing for a more widespread application of these procedures. Theseoperations decrease the invasiveness of the Cox-Maze III procedure, butin evaluating failures, it is often difficult to differentiate whetherthe lesion set was inadequate, or whether the technology was unable tocreate transmural lesions. Lesion patterns that have been studied inanimal models include the original Maze III, the radial incisionsapproach, the tri-ring lesion pattern, and the Star procedure.Alternative patterns include simple bilateral pulmonary vein isolation,the Leipzig lesion pattern, and other patterns.

Alternative ablation technologies may enable surgeons to more widelyoffer curative procedures for atrial fibrillation. Smaller lesionpatterns can be developed from first principals or as a deconstructionof the Maze III or other more extensive pattern. It is possible thatatrial fibrillation begins in most people as a disorder of the leftatrium. Hence, lesions appropriate for paroxysmal atrial fibrillation(pulmonary vein isolation) could be given to patients with chronicatrial fibrillation to prevent recurrence. FIG. 3A illustrates lesions40 effecting isolation of the pulmonary veins PV. These lesions abolishparoxysmal atrial fibrillation. The patterns mentioned above, except theStar procedure and the Leipzig lesion pattern isolate the pulmonaryveins. Intraoperative measurements of pulmonary vein electrograms pre-and post-ablation to insure electrical silence of the muscle sleeveswhere triggers are thought to reside may confirm transmurality duringapplication. Data suggests that in fifty percent of patients, effectivetherapy may be achieved by simply encircling the pulmonary veins withnon-conductive lesions.

Lesion patterns may be tailored for the patient. For example, it hasbeen shown that repetitive electrical activity originates in the leftatrial appendage in patients with mitral valve disease. Electricalisolation of the left atrial appendage should be strongly considered inthese patients. The tri-ring lesion pattern isolates the left atrialappendage, the pulmonary veins, and makes two connecting lesions. Atrialfibrillation associated with right atrial enlargement in congenitalheart disease, or atrial flutter following right atrial incisions incongenital heart procedures do not imply the need for such lesions inthe majority of patients undergoing atrial fibrillation ablation. Theright atrium has a longer effective refractory period than the leftatrium and in general sustains only longer re-entry circuits, the mostcommon being the counterclockwise circuit of typical atrial flutter.This can be ablated by a transmural lesions connecting the tricuspidannulus to the IVC. Additional lesions connecting a lateral rightatriotomy to the IVC or coronary sinus to the IVC may ablate an atypicalright atrial flutter. In general, epicardial ablation may be safer thanendocardial ablation because the energy source is directed into theatrial chamber rather than outward into adjacent mediastinal structures.

If bilateral pulmonary vein isolation is the irreducible component ofsurgical ablation, here is a possible schema for adding additionallesions for a particular patient:

-   -   1. If associated with mitral valve disease, include left atrial        appendage isolation and left atrial appendage connecting lesion.    -   2. If known left atrial flutter (rare) include MV, TV, and LA        appendage connecting lesions.    -   3. If known right atrial flutter, giant right atrium, or planned        right atriotomy, include ablation lesions from TV to IVC;        consider additional lesions from CS to IVC and from atriotomy to        IVC.    -   4. If giant left atrium, consider LA reduction at time of        procedure.

The legion pattern may be based on considerations of safety. There is nolesion pattern that is “best” for all patients, but the leastcomplicated lesion pattern that is safe and easy to deliver and shown tobe effective for a given population can be considered the best for thosepatients.

Referring now to FIG. 3B, a standard Maze III procedure has a lesionpattern 42 in heart H as illustrated. A modified Maze III procedure isillustrated in FIG. 3C, having a lesion pattern 44 applied incryosurgical procedures. In FIG. 3D, a right atrial lesion 46 abolishesatrial flutter that occurs in the right atrium. However, most atrialflutter in the right atrium can be abolished by a single lesion in theisthmus below the OS of the coronary sinus.

Instead of cutting tissue using a Cox-Maze III, or other surgicalprocedure, and rather than invasive destruction of tissue using acryoprobes or the like, radiosurgery system 10 (see FIG. 1) provides theability to target specific foci, regions, lines, and so forthnon-invasively. In a preferred embodiment, one could begin with thepulmonary veins, and then iteratively add additional lesions untilatrial fibrillation is controlled. The exact doses of radiation willlikely differ from patient to patient. A preferred basis for determiningdosage is currently known treatment parameters used to produce lesionsof similar tissues.

Vascular brachytherapy describes endovascular radiation therapy.Brachytherapy describes the application of radioactivity by a sealedsource at a very short distance to the target tissue, e.g., byintracavity or interstitial source placement. The released energy duringtransformation of an unstable atom into a stable atom is absorbed intissue. The quantity of absorbed in a tissue is the “dose” with the SIunit Gray (Gy=J/kg). The dose is strongly dependent on the type ofradiation and the time span, also called “dwell time.” An applicationdose rate is the dose of radiation per time (delivered or received). Thedose rate delivered by a source depends on the activity of the sourceand the radionuclide that it contains. Biological effects of theabsorbed radiation are dependent on the type of radiation and the typeof tissue which is irradiated.

Gamma rays are photons originating from the nucleus of a radionuclide,which take the form of electromagnetic radiation. A heavy unstablenucleus will emit an alpha or beta particle followed by gamma radiation.Gamma rays penetrate deeply within tissues. X-ray radiation iscomparable to gamma radiation. Its physical characteristics are similar,however, its origin is from the electron orbit. Beta radiation comprisesbeta particles, which are lightweight, high-energy electrons with eitherpositive or negative charge. Beta particles can travel only finitedistances within tissue, and when slowed by nuclei interactions theygive rise to high penetration x-rays.

Absorbed radiation can cause damage in tissue either directly byionization or indirectly by interacting with other molecules to producefree radicals which will subsequently damage the target. The target isoften DNA, so that early and late toxic effects in normal tissue aremainly caused by cell death. Both total radiation dose and dose rate areimportant, since damage caused by radiation can be repaired betweenfractionated doses or during low dose rate exposure.

Human aortic cells show a significant decrease in their clonogenicpotential after radiation. In injured vascular tissue, radiation dosesof 12 to 20 Gy appear to efficacious in inhibiting neointimal formation.Possible high dose radiation effects include antiangiogenic effects anddecreases of smooth muscle cells on the adventitia, selectiveinactivation of smooth muscle cells and myofibrolasts or completeelimination of their proliferative capacity at doses above 20 Gy. Lowerdose radiation may promote cellular growth. Hence, promotion of vesselremodeling is dose dependent.

A method for treating a target tissue can be understood with referenceto FIGS. 4 and 5. Method 50 for using system 10 is basically athree-step outpatient procedure which consists of scanning 52, planning54, and treatment 56. Treatment with system 10 begins as the patientundergoes a computer tomography (CT) or magnetic resonance imaging (MRI)as an outpatient. The process may begin with a standard resolution CTscan. MRI scans are optionally used for more accurate tissuedifferentiation. The patient usually leaves the hospital once theimaging is done. The scan is then digitally transferred to the systemtreatment planning workstation. Once the imaging is transferred to aworkstation, the treatment plan is prescribed. A patient considered forsystem by treatment 10 may be assessed extensively by a team comprisedof a treating neurosurgeon, radiation oncologist, and physicist todetermine whether radiation is appropriate and how much. The patient maythen undergo percutaneous placement of fiducials or small radiopaquemarkers that, in conjunction with high quality CT, providethree-dimensional stereotactic localization. The patient then returnsseveral days later for the actual treatment.

On the CT scan, the surgeon and radiation oncologist identify the exactsize, shape and location of the target and the surrounding vitalstructures to be avoided. Once the anatomy has been defined, the systemsoftware determines the number, intensity, and direction of radiationbeams the robot will crossfire in order to insure that a sufficient doseis administered without exceeding the tolerance of the adjacent tissue.The beams are fired from multiple angles. While some of the radiationmay hit surrounding tissues, there is a relatively steep dose gradient.System 10 is capable of treating regions larger than 3-4 cms indiameter. System 10 has been used with motion/respitory trackingsoftware for treating liver and lung tumors where a patient's breathingcould slightly distort the targeting of the tumor.

Sophisticated software allows for complex radiation dose planning inwhich critical structures are identified and protected from harmfullevels of radiation dose. System 10 is capable of irradiating withmillimeter accuracy. System 10 also has the ability to comprehensivelytreat multiple lesions. The patient may undergo open surgery and thenradiosurgery of the non-operative lesions in one hospitalization.

As an example of the capability system 10, a 52 year old woman wasdiagnosed with renal cell carcinoma. She was diagnosed with a largemetastatic lesion and received 3000 cGy external beam irradiation in 10fraction. Her pain continued four months later, associated with a leftradiculopathy. Radiosurgery with system 10 was recommended.

A large lesion was wedged between the patient's remaining left kidneyand the previously irradiated spinal cord. Since the left kidney was heronly remaining kidney, the dose was limited to 200 cGy to the kidney,and 300 cGy to the spinal cord. System 10's robotic capability maximizedthe dose to the tumor and spared the left kidney and spinal cord.

A 30-minute percutaneously fiducial placement procedure was performedone week prior to radiosurgery treatment. The patient was immobilizedand a 30 mm collimator was used to treat with a single fraction to aprescribed dose of 1200 cGy that was calculated to the 80% isodose line.The maximum dosage was 1550 cGy, and the tumor volume was 31.3 cc's.Only 0.252 cc of the spinal cord received greater than 800 cGy.

Treatment was tolerated without difficulty or any discernable acuteeffects and lasted approximately 1 hour. No sedation was necessary andthe patient went home that day. The patient reported a significantimprovement in pain at her one-month follow-up.

In using system 10 to treat atrial fibrillation, the procedure ispre-planned using a 3D image (CAT, MRI, 3D Echo, etc.) of the patient tosequence the direction and intensity of the radiation to cause theclinical effect precisely in the targeted cells with minimal effect tothe surrounding healthy tissue. The typical application relies uponadditive effective up to 50 or more passes at a target, directed fromdifferent directions so that the more superficial and deeper tissuesaround the target receive much lower doses. The accumulative effect ofthe multiple passes may be immediately ablative, or may be sufficientonly to provide coagulation and longer term necrosis.

Advantages of the inventive approach over surgical intervention shouldbe immediately apparent. Surgical approaches are necessarily invasive,and are associated with significant morbidity. The distinction appliesto even more limited surgical procedures for electrical isolation ofdiscreet atrial regions, including for example, atriotomy, RF ablation,and cryoablation. The inventive subject matter discussed herein providesways to perform the ablation of ectopic pathways using focused,image-guided, completely non-invasive methods for energy delivery,effecting a complete treatment without the need for surgery or apercutaneous procedure. The procedure may be offered as an iterativetreatment permitting minimal treatment, until the desired clinicalresult is attained. The procedure, being non-invasive, can be offered asan outpatient procedure without the associated need for an anesthetic orpain medication. Patients needing mitral valve repair concomitantly withatrial fibrillation therapy will likely be an early subset due to thepotential of fiducial marker placement at the time of the valveintervention.

As illustrated in FIG. 4, during a procedure with system 10, a patient Plies still on a treatment table. Generally no sedation or anesthesia isused because the treatment is painless, and the procedure can lastanywhere from between 30 to 90 minutes depending on the complexity ofthe case and the dose to be delivered. The treatment itself involves theadministration of numerous radiation beams delivered from differentdirections, typically in 10 to 15 second bursts. Prior to the deliveryof each radiation beam, a stereo pair of x-ray images is taken by imageguidance system 16 (see FIG. 1) and compared to the original CT scan (orthe like). Between each dose, system 10 uses the information relayedfrom image-guidance system 16 to adjust robotic arm 14 to the movementof the target, which can be caused by anything from blood flow to thepatient breathing. The patient normally leaves the hospital immediatelyafter the treatment is completed, and follow-up imaging is generallypreformed to confirm the treatment. System 10 can administerfractionated radiation therapy over the course of several days. Mostpatients only need one treatment, although some will require treatmentwith several sessions over several days.

Image-guidance technology is of interest for externally appliedradiosurgical techniques to treat cardiac disease. Applicableimage-guidance technologies will improve the accuracy of targeting.Dynamic registration of the patient can account for patient movement,even movement of the heart during pumping and breathing.

Advantageously, the novel treatments described herein can be iterative.Rather than target many foci or regions as is often done in an invasiveprocedure, externally applied radiosurgical techniques can address oneor more focus or regions on one day, and the then other foci or regionson another day as needed. The interim period between treatments can beused to access the need for subsequent treatments. Such iterative orfractionated treatment is thus more conservative than current methods.

Suitable types of radiation, including particle beam radiation, may beemployed. For example, the present invention encompasses the use of aGammaKnife™ radiosurgery system to ablate ectopic pathways in the atria.Although gamma radiation could be administered during open heart orother invasive procedures, the currently preferred applications aresubstantially non-surgical.

All suitable radiosurgery system are contemplated with the energysource, duration and other parameters varying according to a size of thepatient and other factors. A typical GammaKnife™ radiosurgery system maycontain (for example) at least about 200 cobalt-60 sources ofapproximately 30 curies each, all of which are placed in an array undera heavily shielded unit. The shielded unit preferably comprises lead orother heavy metals.

Gamma radiation may be directed to specific target points at a center ofradiation focus. Radiation may be provided during one or more treatmentsessions. For example, a dose of 5000 cGy could be delivered within 20minutes to an effected area defined previously by computer tomography(CT), magnetic resonance imaging (MRI), or angiography.

An image-guided version of a gamma radiation radiosurgery system mayalso be useful. For example, a camera and/or light or other photo devicemay be coupled to a portion of the contemplated gamma radiationradiosurgery system. The heart may be beating during the procedure.

While the exemplary embodiments have been described in some detail, byway of example and for clarity of understanding, those of skill in theart will recognize that a variety of modification, adaptations, andchanges may be employed. For example, multiple energy sources may beemployed, including laser or other photoenergy sources, in combinationwith one or more forms of radiation. Hence, the scope of the presentinvention may be limited solely by the appending claims.

1. A system for treatment of atrial fibrillation in a heart of apatient, the system comprising: a source of particle beam radiation orx-ray radiation; and a robotic system configured for directing theparticle beam radiation or x-ray radiation from outside the patienttoward one or more target treatment regions in the heart so as toinhibit the atrial fibrillation, the robotic system coupled to thesource.
 2. The system of claim 1, wherein the robotic system comprisesan imaging system for imaging a first pulmonary vein and a processorconfigured for targeting the radiation from outside the patient so as toinduce isolation of the first pulmonary vein.
 3. The system of claim 2,wherein the processor is configured to target the radiation so that iteffects bilateral pulmonary vein isolation.
 4. The system of claim 2,wherein the processor is configured to target at least one ectopic focusof the heart for treatment with the radiation.
 5. The system of claim 2,wherein the processor is configured to target the radiation so that theradiation ablates linear lesions within the heart to inhibit an ectopicelectrical pathway, the lesions corresponding to a Maze lesion pattern.6. The system of claim 2, wherein the processor is configured so that afirst portion of the radiation is directed to the patient in a firsttreatment, and a second portion of the radiation is directed to thepatient in a second treatment so that the atrial fibrillation isinhibited in a fractionated radiation procedure allowing assessing ofthe patient between the first treatment and the second treatment.
 7. Thesystem of claim 2, wherein the processor is configured to direct theradiation so as to avoid exceeding a tolerance of tissues adjacent theone or more target regions.
 8. The system of claim 1, wherein therobotic system comprises a robotic arm movably supporting the source anda processor coupled to the robotic arm, the processor configured toeffect delivery of the radiation as a series of radiation beamsextending toward the heart and movement of the robotic arm between beamsso that the beams are directed toward the heart from different angles.9. The system of claim 8, further comprising an imaging system coupledto the processor, wherein the processor is configured to dynamicallyregister the radiation beams with the one or more regions of the heartusing the imaging system.
 10. The system of claim 9, wherein theprocessor is configured to dynamically register so as to compensate forpumping of the heart, movement of the patient, or breathing of thepatient.
 11. The system of claim 9, wherein the processor is configuredto acquire a plurality of target adjustment images from the imagingsystem during a radiation treatment procedure, and to determine aposition of the one or more regions relative to a reference frame of therobot arm from the target adjustment images.
 12. The system of claim 11,further comprising radiopaque fiducial markers suitable for insertioninto the patient around the one or more regions, wherein the imagingsystem comprises first and second fluoroscopic systems.
 13. The systemof claim 12, wherein the target adjustment images are acquired betweendelivery of successive radiation beams.
 14. The system of claim 8,wherein the robot arm moves the source with six degrees of freedom. 15.The system of claim 8, wherein the processor is configured to plan theseries of radiation beams, and wherein the imaging system comprises a CTscanner or an MRI scanner.
 16. The system of claim 15, wherein processorgenerates a plan for the series of radiation beams, the plan comprisinga number of the radiation beams, intensities of the radiation beams, anddirections of the radiation beams.
 17. The system of claim 15, whereinthe target region comprises a non isocentric treatment.
 18. The systemof claim 1, wherein the source comprises a portable linear accelerator,the radiation comprising x-ray radiation.
 19. The system of claim 1,wherein the radiation comprises gamma radiation.
 20. A system fortreatment of atrial fibrillation in a heart of a patient, the systemcomprising: an imaging system for imaging the heart; a radiation sourcefor generating a sequential series of radiation beams from outside thepatient; a robotic arm supporting the radiation source; a processorcoupled to the robotic arm and the source, the processor configured totarget one or more regions of the heart with the radiation so as toinhibit the atrial fibrillation by registering the source outside thepatient with the one or more regions, and transmit a radiation beamtoward the registered one or more region; and wherein the processor isalso configured to repeatedly reposition the robotic arm so as to orientanother radiation beam toward the one or more regions from anotherangle, dynamically register the source with the one or more regions inresponse to the imaging system, and transmit the other radiation beamtoward the dynamically registered one or more region.